PT2139892E - Pirimidodiazepinas substituídas úteis como inibidores da plk1 - Google Patents
Pirimidodiazepinas substituídas úteis como inibidores da plk1 Download PDFInfo
- Publication number
- PT2139892E PT2139892E PT08717594T PT08717594T PT2139892E PT 2139892 E PT2139892 E PT 2139892E PT 08717594 T PT08717594 T PT 08717594T PT 08717594 T PT08717594 T PT 08717594T PT 2139892 E PT2139892 E PT 2139892E
- Authority
- PT
- Portugal
- Prior art keywords
- acid
- compound
- plk1
- cyclopentyl
- mole
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 3
- OHXQYFCNXHGKPJ-UHFFFAOYSA-N 1h-pyrimido[5,4-c]diazepine Chemical class N1N=CC=CC2=NC=NC=C12 OHXQYFCNXHGKPJ-UHFFFAOYSA-N 0.000 title 1
- 101150073897 plk1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- DJNZZLZKAXGMMC-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound COC1=CC(C(=O)NC2CCN(C)CC2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)C(F)(F)CN2C1CCCC1 DJNZZLZKAXGMMC-UHFFFAOYSA-N 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 208000037841 lung tumor Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000023958 prostate neoplasm Diseases 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- -1 invert sugar Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 13
- 108010056274 polo-like kinase 1 Proteins 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- XQSNXLDLKOJJOU-UHFFFAOYSA-N pyrimido[5,4-c]diazepin-3-one Chemical compound N1=NC(=O)C=CC2=NC=NC=C21 XQSNXLDLKOJJOU-UHFFFAOYSA-N 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- DQJHTCZROXSXEZ-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=NC=C(N(C)C(=O)C(F)(F)CN2C3CCCC3)C2=N1 DQJHTCZROXSXEZ-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 229940123237 Taxane Drugs 0.000 description 3
- 229940122803 Vinca alkaloid Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- UXNKBIRHIGVUMN-UHFFFAOYSA-N ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate Chemical compound CCOC(=O)C(F)(F)CNC1CCCC1 UXNKBIRHIGVUMN-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- QUCPBKFOMWSJFG-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7,7-difluoro-5,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)C(F)(F)CN1C1CCCC1 QUCPBKFOMWSJFG-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229910052693 Europium Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000729945 Homo sapiens Serine/threonine-protein kinase PLK2 Proteins 0.000 description 2
- 101000691614 Homo sapiens Serine/threonine-protein kinase PLK3 Proteins 0.000 description 2
- 101000582914 Homo sapiens Serine/threonine-protein kinase PLK4 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102100031462 Serine/threonine-protein kinase PLK2 Human genes 0.000 description 2
- 102100026209 Serine/threonine-protein kinase PLK3 Human genes 0.000 description 2
- 102100030267 Serine/threonine-protein kinase PLK4 Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 150000001576 beta-amino acids Chemical class 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000025084 cell cycle arrest Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000006618 mitotic catastrophe Effects 0.000 description 2
- PGFULZFLPKLOGP-UHFFFAOYSA-N n-(benzotriazol-1-ylmethyl)cyclopentanamine Chemical compound N1=NC2=CC=CC=C2N1CNC1CCCC1 PGFULZFLPKLOGP-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000000771 oncological effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 1
- OFCBNMYNAHUDGE-UHFFFAOYSA-N 2-chloro-5-nitropyrimidine Chemical class [O-][N+](=O)C1=CN=C(Cl)N=C1 OFCBNMYNAHUDGE-UHFFFAOYSA-N 0.000 description 1
- AHJZAWIFZSBGKJ-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C1C(F)(F)C(=O)N(C)C2=CN=C(Cl)N=C2N1C1CCCC1 AHJZAWIFZSBGKJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- DPMYMKIUVFYCKZ-UHFFFAOYSA-N ClC1=NC=C(C(=N1)N(CC(C(=O)O)(F)F)C1CCCC1)[N+](=O)[O-] Chemical compound ClC1=NC=C(C(=N1)N(CC(C(=O)O)(F)F)C1CCCC1)[N+](=O)[O-] DPMYMKIUVFYCKZ-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 description 1
- 101100408813 Drosophila melanogaster polo gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 230000037060 G2 phase arrest Effects 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Chemical class 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930182558 Sterol Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- HYZHPAXFOXQGMV-UHFFFAOYSA-N benzotriazol-1-ylmethanamine Chemical class C1=CC=C2N(CN)N=NC2=C1 HYZHPAXFOXQGMV-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 description 1
- ZKJVOFNXVHNODR-UHFFFAOYSA-N ethyl 3-[(2-chloro-5-nitropyrimidin-4-yl)-cyclopentylamino]-2,2-difluoropropanoate Chemical compound N=1C(Cl)=NC=C([N+]([O-])=O)C=1N(CC(F)(F)C(=O)OCC)C1CCCC1 ZKJVOFNXVHNODR-UHFFFAOYSA-N 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- OEGVADJWEKHZCC-UHFFFAOYSA-N methyl 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoate Chemical compound CN1C2=CN=C(N=C2N(CC(C1=O)(F)F)C3CCCC3)NC4=C(C=C(C=C4)C(=O)OC)OC OEGVADJWEKHZCC-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000011911 α-alkylation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91935807P | 2007-03-22 | 2007-03-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2139892E true PT2139892E (pt) | 2011-11-21 |
Family
ID=39415299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT08717594T PT2139892E (pt) | 2007-03-22 | 2008-03-11 | Pirimidodiazepinas substituídas úteis como inibidores da plk1 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7517873B2 (https=) |
| EP (1) | EP2139892B1 (https=) |
| JP (1) | JP5087640B2 (https=) |
| KR (1) | KR101157848B1 (https=) |
| CN (2) | CN102746175B (https=) |
| AR (1) | AR065794A1 (https=) |
| AT (1) | ATE524472T1 (https=) |
| AU (1) | AU2008228303B2 (https=) |
| BR (1) | BRPI0809088A2 (https=) |
| CA (1) | CA2680757A1 (https=) |
| CL (1) | CL2008000785A1 (https=) |
| CY (1) | CY1112102T1 (https=) |
| DK (1) | DK2139892T3 (https=) |
| ES (1) | ES2371832T3 (https=) |
| HR (1) | HRP20110807T1 (https=) |
| IL (1) | IL200617A (https=) |
| MX (1) | MX2009010034A (https=) |
| PE (1) | PE20120495A1 (https=) |
| PL (1) | PL2139892T3 (https=) |
| PT (1) | PT2139892E (https=) |
| SI (1) | SI2139892T1 (https=) |
| TW (1) | TWI363629B (https=) |
| WO (1) | WO2008113711A1 (https=) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015117087A1 (en) | 2014-01-31 | 2015-08-06 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| US9975896B2 (en) | 2013-07-25 | 2018-05-22 | Dana-Farber Cancer Institute, Inc. | Inhibitors of transcription factors and uses thereof |
| US10150756B2 (en) | 2014-01-31 | 2018-12-11 | Dana-Farber Cancer Institute, Inc. | Diaminopyrimidine benzenesulfone derivatives and uses thereof |
| US10308653B2 (en) | 2014-08-08 | 2019-06-04 | Dana-Farber Cancer Institute, Inc. | Diazepane derivatives and uses thereof |
| US10702527B2 (en) | 2015-06-12 | 2020-07-07 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| US10881668B2 (en) | 2015-09-11 | 2021-01-05 | Dana-Farber Cancer Institute, Inc. | Acetamide thienotriazolodiazepines and uses thereof |
| US10913752B2 (en) | 2015-11-25 | 2021-02-09 | Dana-Farber Cancer Institute, Inc. | Bivalent bromodomain inhibitors and uses thereof |
| US11306105B2 (en) | 2015-09-11 | 2022-04-19 | Dana-Farber Cancer Institute, Inc. | Cyano thienotriazolodiazepines and uses thereof |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008287339A1 (en) * | 2007-08-15 | 2009-02-19 | Vertex Pharmaceuticals Incorporated | 4-(9-(3, 3-difluorocyclopentyl) -5, 7, 7-trimethyl-6-oxo-6, 7, 8, 9-tetrahydro-5H-pyrimido [4, 5-b][1, 4] diazepin-2-ylamino)-3-methoxybenzamide Derivatives as Inhibitors of the Human Protein Kinases PLK1 to PLK4 for the Treatment of Proliferative Diseases |
| EP2205241B1 (en) * | 2007-09-25 | 2014-05-21 | Takeda Pharmaceutical Company Limited | Polo-like kinase inhibitors |
| PL2205603T3 (pl) | 2007-09-28 | 2014-07-31 | Cyclacel Ltd | Pochodne pirymidyny jako inhibitory kinaz białkowych |
| US20090291938A1 (en) * | 2007-11-19 | 2009-11-26 | Takeda Pharmaceutical Company Limited | Polo-like kinase inhibitors |
| TWI490214B (zh) | 2008-05-30 | 2015-07-01 | 艾德克 上野股份有限公司 | 苯或噻吩衍生物及該等作為ｖａｐ－１抑制劑之用途 |
| EP2303889A1 (en) * | 2008-06-18 | 2011-04-06 | F. Hoffmann-La Roche AG | Halo-substituted pyrimidodiazepines as plkl inhibitors |
| RS53347B (sr) | 2008-12-09 | 2014-10-31 | Gilead Sciences, Inc. | Modulatori toll-sličnih receptora |
| EP3828185B1 (en) | 2009-01-06 | 2024-11-20 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders |
| LT3141252T (lt) | 2009-06-17 | 2018-11-12 | Vertex Pharmaceuticals Inc. | Gripo virusų replikacijos inhibitoriai |
| CA2772253C (en) | 2009-09-14 | 2018-02-27 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| RU2013132681A (ru) | 2010-12-16 | 2015-01-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы репликации вирусов гриппа |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| WO2014145909A2 (en) | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone compounds and methods of treating disorders |
| TWI652014B (zh) | 2013-09-13 | 2019-03-01 | 美商艾佛艾姆希公司 | 雜環取代之雙環唑殺蟲劑 |
| LT3068776T (lt) | 2013-11-13 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Gripo virusų replikacijos inhibitoriai |
| JP6618901B2 (ja) | 2013-11-13 | 2019-12-11 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
| JP6522732B2 (ja) | 2014-07-11 | 2019-05-29 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖを治療するためのトール様受容体の調節因子 |
| SG11201701520TA (en) | 2014-09-16 | 2017-04-27 | Gilead Sciences Inc | Solid forms of a toll-like receptor modulator |
| KR102306860B1 (ko) | 2014-09-16 | 2021-09-30 | 길리애드 사이언시즈, 인코포레이티드 | 톨-유사 수용체 조정제를 제조하는 방법 |
| EP3294735B8 (en) | 2015-05-13 | 2022-01-05 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| EP3294717B1 (en) | 2015-05-13 | 2020-07-29 | Vertex Pharmaceuticals Inc. | Methods of preparing inhibitors of influenza viruses replication |
| KR20180132812A (ko) * | 2016-04-07 | 2018-12-12 | 다나-파버 캔서 인스티튜트 인크. | 피리미도-디아제피논 키나아제 스캐폴드 화합물 및 ｐｉ3ｋ-매개된 장애의 치료 방법 |
| TWI810456B (zh) | 2019-05-22 | 2023-08-01 | 美商基利科學股份有限公司 | Tlr7調節化合物及hiv疫苗之組合 |
| US12551563B2 (en) | 2019-09-27 | 2026-02-17 | Dana-Farber Cancer Institute, Inc. | ERK5 degraders as therapeutics in cancer and inflammatory diseases |
| KR20210122163A (ko) * | 2020-03-27 | 2021-10-08 | (주) 업테라 | Plk1의 선택적 분해를 유도하는 피라졸로퀴나졸린 유도체 화합물 |
| WO2022145989A1 (ko) * | 2020-12-31 | 2022-07-07 | (주) 업테라 | 선택적 plk1 억제제로서의 피리미도디아제핀 유도체 |
| PE20240894A1 (es) * | 2021-08-10 | 2024-04-24 | Uppthera Inc | Compuesto inductor de la degradacion de plk1 novedoso |
| GB202313514D0 (en) | 2023-09-05 | 2023-10-18 | Cambridge Entpr Ltd | Treatment of inflammatory diseases |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA02002938A (es) * | 1999-09-17 | 2004-12-06 | Abbott Gmbh & Co Kg | Inhibidores de cinasa como agentes agentes terapeuticos. |
| UA76512C2 (en) * | 2001-09-04 | 2006-08-15 | Boehringer Ingelheim Pharma | Dihydropteridinones, a method for producing thereof and use thereof as medicament |
| US7622463B2 (en) * | 2006-02-14 | 2009-11-24 | Vertex Pharmaceuticals Incorporated | Dihydrodiazepines useful as inhibitors of protein kinases |
| TW200808325A (en) * | 2006-07-06 | 2008-02-16 | Astrazeneca Ab | Novel compounds |
-
2008
- 2008-03-11 AU AU2008228303A patent/AU2008228303B2/en not_active Ceased
- 2008-03-11 WO PCT/EP2008/052847 patent/WO2008113711A1/en not_active Ceased
- 2008-03-11 BR BRPI0809088-2A patent/BRPI0809088A2/pt not_active IP Right Cessation
- 2008-03-11 HR HR20110807T patent/HRP20110807T1/hr unknown
- 2008-03-11 PT PT08717594T patent/PT2139892E/pt unknown
- 2008-03-11 EP EP08717594A patent/EP2139892B1/en not_active Not-in-force
- 2008-03-11 MX MX2009010034A patent/MX2009010034A/es active IP Right Grant
- 2008-03-11 KR KR1020097019761A patent/KR101157848B1/ko not_active Expired - Fee Related
- 2008-03-11 SI SI200830445T patent/SI2139892T1/sl unknown
- 2008-03-11 JP JP2009553997A patent/JP5087640B2/ja not_active Expired - Fee Related
- 2008-03-11 CA CA002680757A patent/CA2680757A1/en not_active Abandoned
- 2008-03-11 DK DK08717594.9T patent/DK2139892T3/da active
- 2008-03-11 PL PL08717594T patent/PL2139892T3/pl unknown
- 2008-03-11 AT AT08717594T patent/ATE524472T1/de active
- 2008-03-11 CN CN201210030872.3A patent/CN102746175B/zh not_active Expired - Fee Related
- 2008-03-11 ES ES08717594T patent/ES2371832T3/es active Active
- 2008-03-11 CN CN2008800088890A patent/CN101636399B/zh not_active Expired - Fee Related
- 2008-03-18 CL CL2008000785A patent/CL2008000785A1/es unknown
- 2008-03-19 US US12/051,000 patent/US7517873B2/en not_active Expired - Fee Related
- 2008-03-19 PE PE2011001933A patent/PE20120495A1/es not_active Application Discontinuation
- 2008-03-19 AR ARP080101142A patent/AR065794A1/es unknown
- 2008-03-19 TW TW097109660A patent/TWI363629B/zh not_active IP Right Cessation
-
2009
- 2009-08-27 IL IL200617A patent/IL200617A/en not_active IP Right Cessation
-
2011
- 2011-11-30 CY CY20111101174T patent/CY1112102T1/el unknown
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9975896B2 (en) | 2013-07-25 | 2018-05-22 | Dana-Farber Cancer Institute, Inc. | Inhibitors of transcription factors and uses thereof |
| WO2015117087A1 (en) | 2014-01-31 | 2015-08-06 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| EP3099693A4 (en) * | 2014-01-31 | 2017-08-16 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| US10150756B2 (en) | 2014-01-31 | 2018-12-11 | Dana-Farber Cancer Institute, Inc. | Diaminopyrimidine benzenesulfone derivatives and uses thereof |
| US10730860B2 (en) | 2014-01-31 | 2020-08-04 | Dana-Farber Cancer Institute, Inc. | Diaminopyrimidine benzenesulfone derivatives and uses thereof |
| US10308653B2 (en) | 2014-08-08 | 2019-06-04 | Dana-Farber Cancer Institute, Inc. | Diazepane derivatives and uses thereof |
| US10702527B2 (en) | 2015-06-12 | 2020-07-07 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| US10881668B2 (en) | 2015-09-11 | 2021-01-05 | Dana-Farber Cancer Institute, Inc. | Acetamide thienotriazolodiazepines and uses thereof |
| US11306105B2 (en) | 2015-09-11 | 2022-04-19 | Dana-Farber Cancer Institute, Inc. | Cyano thienotriazolodiazepines and uses thereof |
| US11406645B2 (en) | 2015-09-11 | 2022-08-09 | Dana-Farber Cancer Institute, Inc. | Acetamide thienotriazolodiazepines and uses thereof |
| US10913752B2 (en) | 2015-11-25 | 2021-02-09 | Dana-Farber Cancer Institute, Inc. | Bivalent bromodomain inhibitors and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| SI2139892T1 (sl) | 2011-12-30 |
| PE20120495A1 (es) | 2012-05-12 |
| IL200617A (en) | 2014-02-27 |
| CN101636399B (zh) | 2012-04-18 |
| PL2139892T3 (pl) | 2012-03-30 |
| TW200843781A (en) | 2008-11-16 |
| CN102746175A (zh) | 2012-10-24 |
| CN102746175B (zh) | 2014-01-15 |
| US7517873B2 (en) | 2009-04-14 |
| US20080234255A1 (en) | 2008-09-25 |
| AU2008228303A1 (en) | 2008-09-25 |
| IL200617A0 (en) | 2010-05-17 |
| KR101157848B1 (ko) | 2012-07-11 |
| KR20090119913A (ko) | 2009-11-20 |
| AU2008228303B2 (en) | 2012-04-19 |
| DK2139892T3 (da) | 2011-12-12 |
| EP2139892B1 (en) | 2011-09-14 |
| JP5087640B2 (ja) | 2012-12-05 |
| JP2010521514A (ja) | 2010-06-24 |
| EP2139892A1 (en) | 2010-01-06 |
| BRPI0809088A2 (pt) | 2014-09-09 |
| HRP20110807T1 (hr) | 2011-12-31 |
| ATE524472T1 (de) | 2011-09-15 |
| HK1139936A1 (en) | 2010-09-30 |
| CL2008000785A1 (es) | 2009-03-27 |
| CN101636399A (zh) | 2010-01-27 |
| CA2680757A1 (en) | 2008-09-25 |
| AR065794A1 (es) | 2009-07-01 |
| WO2008113711A1 (en) | 2008-09-25 |
| ES2371832T3 (es) | 2012-01-10 |
| MX2009010034A (es) | 2009-10-12 |
| TWI363629B (en) | 2012-05-11 |
| CY1112102T1 (el) | 2015-11-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT2139892E (pt) | Pirimidodiazepinas substituídas úteis como inibidores da plk1 | |
| CN106488910B (zh) | Kras g12c的抑制剂 | |
| WO2021252339A1 (en) | Substituted purine-2,6-dione compounds as kras inhibitors | |
| CA2905993C (en) | Substituted 4-amino-pyrimidinyl-2-amino-phenyl derivatives and pharmaceutical compositions thereof for use as jak2 and alk2 inhibitors | |
| ES2448868T3 (es) | Metabolitos del inhibidor de cinasas Janus (R)-3-(4-(7H-pirrolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopentilpropanonitrilo | |
| US8609650B2 (en) | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as Axl inhibitors | |
| JP7200120B2 (ja) | Ｍｋ２阻害剤として有用なヘテロアリール化合物 | |
| AU2018352695A1 (en) | Benzimidazole-indole inhibitors of Mnk1 and Mnk2 | |
| SK4622002A3 (en) | Tert.-butyl-(7-methyl-imidazo[1,2-a]pyridine-3-yl)-amine derivatives, method for producing thereof and medicaments comprising said compounds | |
| WO2018045142A1 (en) | Immune checkpoint inhibitors, compositions and methods thereof | |
| WO2008022164A2 (en) | Pyrazine compounds, their use and methods of preparation | |
| JP2012500802A (ja) | プロリルヒドロキシラーゼ阻害剤 | |
| EA021595B1 (ru) | Пиримидиноны в качестве ингибиторов pi3k | |
| WO2018170201A1 (en) | Deuterated analogs of mk2 inhibitors and uses thereof | |
| EA034440B1 (ru) | СОЕДИНЕНИЯ ПИРРОЛО-, ПИРАЗОЛО-, ИМИДАЗОПИРИМИДИНА И ПИРИДИНА, КОТОРЫЕ ИНГИБИРУЮТ Mnk1 И Mnk2 | |
| WO2015058661A1 (zh) | Bcr-abl激酶抑制剂及其应用 | |
| CN1893944B (zh) | 具有抗增殖活性的3-氰基喹啉衍生物 | |
| EP4450503A1 (en) | Aromatic heterocyclic compounds, preparation method therefor and uses thereof | |
| US12116348B2 (en) | Substituted benzimidazole compound and composition comprising same | |
| EP4293029B1 (en) | Azaheteroaryl compound, preparation method therefor, and application thereof | |
| US20160297824A1 (en) | Imidazo-fused heterocycles and uses thereof | |
| US20220362245A1 (en) | Compounds for inhibiting fgfr4 | |
| WO2023070053A1 (en) | Inhibitors of raf kinases | |
| EP3816162B1 (en) | Diarylpyrazole compound, composition comprising same, and use thereof | |
| WO2022171126A1 (zh) | 作为Wee-1抑制剂的稠环化合物 |